Further analysis of the antinociceptive action caused by p-methoxyl-diphenyl diselenide in mice.
The objective of this study was to extend our previous findings by investigating in greater detail the mechanisms that might be involved in the antinociceptive action of p-methoxyl-diphenyl diselenide, (MeOPhSe)(2), in mice. The pretreatment with nitric oxide precursor, l-arginine (600 mg/kg, intraperitoneal, i.p.), reversed antinociception caused by (MeOPhSe)(2) (10 mg/kg, p.o.) or N(G)-nitro-l-arginine (l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT(3) receptor antagonist) and SCH23390 (0.05 mg/kg, i.p.., a D(1) receptor antagonist) blocked the antinociceptive effect caused by (MeOPhSe)(2). Conversely, pindolol (1 mg/kg, i.p., a 5-HT(1A)/(1B) receptor/beta adrenoceptor antagonist), WAY 100635 (0.7 mg/kg, i.p., a selective 5-HT(1A) receptor antagonist), ketanserin (0.3 mg/kg, i.p., a selective 5-HT(2A) receptor antagonist), prazosin (0.15 mg/kg, i.p., an alpha(1)-adrenoreceptor antagonist), yohimbine (1.0 mg/kg, i.p., an alpha(2)-adrenoreceptor antagonist), sulpiride (5 mg/kg, i.p., a D(2) receptor antagonist), naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) and caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist) did not change the antinociceptive effect of (MeOPhSe)(2). (MeOPhSe)(2) significantly inhibited nociception induced by intraplantar (i.pl.) injection of bradykinin (10 nmol/paw) and Des-Arg(9)-bradykinin (10 nmol/paw, a B(1) receptor agonist). (MeOPhSe)(2) significantly inhibited phorbol myristate acetate (PMA, 0.03 mug/paw, a protein kinase C (PKC) activator)-induced licking response. These results indicate that (MeOPhSe)(2) produced antinociception in mice through mechanisms that involve an interaction with nitrergic system, 5-HT(3) and D(1) receptors. The antinociceptive effect is related to (MeOPhSe)(2) ability to interact with kinin B(1) and B(2) receptors and PKC pathway mediated mechanisms.
Jesse
Cristiano R
CR
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.
Rocha
Joao B T
JB
Nogueira
Cristina W
CW
Savegnago
Lucielli
L
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate
D000700:Analgesics; D001552:Benzazepines; D001555:Benzene Derivatives; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D016566:Organoselenium Compounds; D017981:Receptors, Neurotransmitter; C534628:SCH 23390; C528548:p-methoxy-diphenyl diselenide; C046722:bradykinin, des-Arg(1)-; D019335:Nitroarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin